Alain J De Solis, Almudena Del Río-Martín, Jan Radermacher, Weiyi Chen, Lukas Steuernagel, Corinna A Bauder, Fynn R Eggersmann, Donald A Morgan, Anna-Lena Cremer, Michael Sué, Maximilian Germer, Christian Kukat, Stefan Vollmar, Heiko Backes, Kamal Rahmouni, Peter Kloppenburg, Jens C Brüning
Agouti-related peptide (AgRP)-expressing and proopiomelanocortin (POMC)-expressing neurons reciprocally regulate food intake. Here, we combine non-interacting recombinases to simultaneously express functionally opposing chemogenetic receptors in AgRP and POMC neurons for comparing metabolic responses in male and female mice with simultaneous activation of AgRP and inhibition of POMC neurons with isolated activation of AgRP neurons or isolated inhibition of POMC neurons. We show that food intake is regulated by the additive effect of AgRP neuron activation and POMC neuron inhibition, while systemic insulin sensitivity and gluconeogenesis are differentially modulated by isolated-versus-simultaneous regulation of AgRP and POMC neurons...
February 20, 2024: Nature metabolism